Manipulating fluidic reagents and assessing the results of reagent interactions are central to chemical and biological science. Manipulations include mixing fluidic reagents, assaying products resulting from such mixtures, separation or purification of products and reagents, and the like. A single experiment may involve hundreds of fluidic manipulations, product separations, recording processes and the like, each of which involve different types of laboratory equipment and conditions.
One particularly labor intensive biochemical series of laboratory fluidic manipulations is nucleic acid synthesis and analysis. A variety of in vitro amplifications methods for biochemical synthesis of nucleic acids are available, such as the polymerase chain reaction (PCR). See, Mullis et al., (1987) U.S. Pat. No. 4,683,202 and PCR protocols: A Guide to Methods and Applications (Innis et al. eds., Academic Press Inc. San Diego Calif. (1990). PCR methods typically require the use of specialized machinery for performing thermocycling reactions for DNA synthesis followed by the use of special machinery for the electrophoretic analysis of synthesized nucleic acids.
Various strategies have been used to increase laboratory throughput. For example, microscale devices for high throughput mixing and assaying small fluid volumes have been developed. See, e.g., Parce et al., U.S. Pat. No. 5,942,443, which provides pioneering technology related to microscale devices. In particular, U.S. Pat. No. 6,306,590 provides methods of performing PCR and nucleic acid separations in the same microfluidic device.
Improved methods for performing PCR and nucleic acid separations including improved sieving mediums are desirable, particularly those which take advantage of high-throughput, low cost microfluidic systems. The present invention provides these and other features by providing nucleic acid sieving mediums, methods of performing PCR and nucleic acid separations along with high throughput microscale systems and many other features that will be apparent upon complete review of the following disclosure.